Our central thesis is that antigens with few determinants are preferential inducers of cellular immunity. Evidence suggests that one function of mycobacterial adjuvant is to activate macrophages thereby increasing their digestive abilities for antigens, fragmenting these into entities which induce cellular immunity. Procedures for examining this possibility are: (1) Complex antigens injected into the site of a dermal delayed response to an unrelated antigen result in striking levels of hypersensitivity to the injected antigen. The mechanism may be in local processing of the injected antigen by activated macrophages, to be examined with cells in vitro. (2) A mouse tumor line shows enhanced protective immunogenicity when incubated in vitro with mouse macrophages preactivated by mycobacteria. Efforts will be made to dissociate antigenic fragments from macrophage membranes (chloral hydrate) and to correlate sizes of fragments with immunogenicity. (3) analogous studies will be made with sheep red blood cells and pneumococcal II polysaccharide, with which similar results have been found. (4) The mode of action of water- soluble mycobacterial adjuvant will be tested by their activities in vitro on macrophages (glucose metabolism, lysosome formation and hydrolases, mitogenicity for T and B lymphocytes, and alterations in contents of cyclic nuclotides, using stimulators and inhibitors of cAMP and cGMP. (5) Efforts will continue to find whether conjugation to a multivalent carrier of a simple antigenic determinant, the myelin nonapeptide that induces allergic encephalomyelitis, may preferentially induce antibodies. Carriers so far used (maleic anhydride and poly-L- lysine) have provided partial evidence for this. Better controlled attachment of peptide to carrier may resolve this question, which is the obverse of the thesis that simple antigens per se are better evokers of cellular immunity.